Skip to main content
Log in

Exogenous procalcitonin evokes a pro-inflammatory cytokine response

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective and design

Procalcitonin (ProCT) is increased in serum of septic patients and those with systemic inflammation. Endogenous levels of ProCT might influence the response of polymorphonuclear leukocytes (PMNs), independently of endotoxin, in clinical disease.

Subjects

Healthy human volunteers.

Treatment

Recombinant human ProCT (rhProCT).

Methods

Whole blood and PMNs were exposed in vitro to exogenous rhProCT. Interleukin (IL)-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNFα), IL-1β, and macrophage inflammatory protein (MIP)-1β (pg/ml) were measured by multiplex suspension bead-array immunoassay, and migration and phagocytosis were measured in PMNs.

Results

In a whole-blood model, a dose-dependent increase in IL-6, TNFα, and IL-1β of the cell-free supernatant was noted. Pre-incubation with ProCT, at doses consistent with clinical sepsis, resulted in a decrease in PMN migration without alteration in phagocytosis of Staphylococcus aureus or indirect measurements of bacterial killing.

Conclusion

Clinically relevant levels of ProCT influence immunologic responses that may contribute to systemic inflammatory response and septic shock.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008;36(3):941–52.

    Article  CAS  PubMed  Google Scholar 

  2. Muller B, White JC, Nylen ES, Snider RH, Becker KL, Habener JF. Ubiquitous expression of the calcitonin-gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab. 2001;86(1):396–404.

    Article  CAS  PubMed  Google Scholar 

  3. Wenisch C, Fladerer P, Patruta S, Krause R, Horl W. Assessment of neutrophil function in patients with septic shock: comparison of methods. Clin Diagn Lab Immunol. 2001;8(1):178–80.

    CAS  PubMed  Google Scholar 

  4. Chishti AD, Shenton BK, Kirby JA, Baudouin SV. Neutrophil chemotaxis and receptor expression in clinical septic shock. Intensive Care Med. 2004;30(4):605–11.

    Article  PubMed  Google Scholar 

  5. Vespasiano MC, Lewandoski JR, Zimmerman JJ. Longitudinal analysis of neutrophil superoxide anion generation in patients with septic shock. Crit Care Med. 1993;21(5):666–72.

    Article  CAS  PubMed  Google Scholar 

  6. Tavares-Murta BM, Zaparoli M, Ferreira RB, Silva-Vergara ML, Oliveira CH, Murta EF, et al. Failure of neutrophil chemotactic function in septic patients. Crit Care Med. 2002;30(5):1056–61.

    Article  PubMed  Google Scholar 

  7. Wiedermann FJ, Kaneider N, Egger P, Tiefenthaler W, Wiedermann CJ, Lindner KH, Schobersberger W. Migration of human monocytes in response to procalcitonin. Crit Care Med. 2002;30(5):1112–7.

    Article  CAS  PubMed  Google Scholar 

  8. Monneret G, Arpin M, Venet F, Maghni K, Debard AL, Pachot A, et al. Calcitonin gene related peptide and N-procalcitonin modulate CD11b upregulation in lipopolysaccharide activated monocytes and neutrophils. Intensive Care Med. 2003;29(6):923–8.

    PubMed  Google Scholar 

  9. Nylen ES, Whang KT, Snider RH Jr, Steinwald PM, White JC, Becker KL. Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis. Crit Care Med. 1998;26(6):1001–6.

    Article  CAS  PubMed  Google Scholar 

  10. Steinwald PM, Whang KT, Becker KL, Snider RH, Nylen ES, White JC. Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis. Crit Care. 1999;3(1):11–6.

    Article  PubMed  Google Scholar 

  11. Martinez JM, Wagner KE, Snider RH, Nylen ES, Muller B, Sarani B, et al. Late immunoneutralization of procalcitonin arrests the progression of lethal porcine sepsis. Surg Infect (Larchmt). 2001;2(3):193–202.

    Article  CAS  Google Scholar 

  12. Becker KL, Nylen ES, Snider RH, Muller B, White JC. Immunoneutralization of procalcitonin as therapy of sepsis. J Endotoxin Res. 2003;9(6):367–74.

    CAS  PubMed  Google Scholar 

  13. Sexton PM, Christopoulos G, Christopoulos A, Nylen ES, Snider RH Jr, Becker KL. Procalcitonin has bioactivity at calcitonin receptor family complexes: potential mediator implications in sepsis. Crit Care Med. 2008;36(5):1637–40.

    Article  CAS  PubMed  Google Scholar 

  14. Gomes RN, Castro-Faria-Neto HC, Bozza PT, Soares MB, Shoemaker CB, David JR, et al. Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia. Shock. 2005;24(6):590–4.

    Article  CAS  PubMed  Google Scholar 

  15. Whang KT, Vath SD, Becker KL, Snider RH, Nylen ES, Muller B, et al. Procalcitonin and proinflammatory cytokine interactions in sepsis. Shock. 2002;14(1):73–8.

    Article  Google Scholar 

  16. Wei JX, Verity A, Garle M, Mahajan R, Wilson V. Examination of the effect of procalcitonin on human leucocytes and the porcine isolated coronary artery. Br J Anaesth. 2008;100(5):612–21.

    Article  CAS  PubMed  Google Scholar 

  17. Sato Y. Modulation of PMN-endothelial cells interactions by cyclic nucleotides. Curr Pharm Des. 2004;10(2):163–70.

    Article  CAS  PubMed  Google Scholar 

  18. Lennon PF, Taylor CT, Stahl GL, Colgan SP. Neutrophil-derived 5′-adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A2B receptor activation. J Exp Med. 1998;188(8):1433–43.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Angelike P. Liappis.

Additional information

Responsible Editor: Artur Bauhofer.

The views expressed in this article are those of the authors and do not necessarily reflect the policies of the Department of Veterans Affairs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liappis, A.P., Gibbs, K.W., Nylen, E.S. et al. Exogenous procalcitonin evokes a pro-inflammatory cytokine response. Inflamm. Res. 60, 203–207 (2011). https://doi.org/10.1007/s00011-010-0255-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-010-0255-8

Keywords

Navigation